The global hypothesis of this program project grant(PPG) is to test whether genetic abnormalities deregulate p53/cell cycle control leading to transformed clones that initiate lung cancer. This hypothesis will be tested in patient samples and animal models. There are 5 projects in this PPG. The specific aims are 1) to analyze the preneoplastic dysplastic lesions of the smoker's bronchial epithelium to correlate in vivo p53 DNA adducts and p53 hot spot mutations, 2) model the molecular mutations and deletions found in lung cancers in lung-specific transgenic mice, and 3) devlop adenoviral and Sinbis vectors to target lung cancer cells and induce cell death. The Core Laboratory was utilized for BAL, ELISA, laminar flow hood, Northern analysis, oligonucleotide synthesis, PCR, Recombinant DNA techniques, Southern analysis, ultracentrifugation, and Western analysis.